P Thul, L Åkesson, M Wiking, D Mahdessian, H AitBlal, A Bäckström, F Danielsson, C Gnann, M Hjelmare, R Schutten, C Stadler, D Sullivan, C Winsnes, M Uhlén, E Lundberg
SciLifeLab, Royal Institute of Technology (KTH), Stockholm, Sweden
Compartmentalization of biological reactions is an important mechanism to allow multiple cellular reactions to occur in parallel. Resolving the spatial distribution of the human proteome at a subcellular level increases our understanding of human biology and disease. A high-resolution map of the human cell has been generated, the Cell Atlas, part of the open access Human Protein Atlas database (1,2). Using an antibody and imaging-based approach 12,003 proteins have been localized to 32 subcellular structures, enabling the definition of 13 major organelle proteomes. The high spatial resolution allowed identification of novel protein components of fine structures such as the midbody and nuclear bodies. An integrative approach includes strict validation criteria using gene silencing, paired antibodies, and fluorescently tagged proteins (3,4).
We show that half of all proteins localize to multiple compartments. On one level, it can be a spatial confinement to control the timing of the molecular function in one compartment. On another level, such proteins may have context specific functions and ‘moonlight’ in different parts of the cell, thus increasing the functionality of the proteome and the complexity of the cell from a systems perspective. We further reveal 16% of the proteome to show single cell expression variation in terms of protein abundance or spatial distribution. Finally we show that current protein-protein network models benefit from integration of the Cell Atlas localization data as spatial boundaries.
Here we discuss the importance of spatial proteomics for single cell biology, including the citizen science effort “Project Discovery”(5) and present the content of the HPA Cell Atlas.